RT Journal Article
SR Electronic
T1 RFWD3 and translesion DNA polymerases contribute to PCNA modification–dependent DNA damage tolerance
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201584
DO 10.26508/lsa.202201584
VO 5
IS 12
A1 Kanao, Rie
A1 Kawai, Hidehiko
A1 Taniguchi, Toshiyasu
A1 Takata, Minoru
A1 Masutani, Chikahide
YR 2022
UL https://www.life-science-alliance.org/content/5/12/e202201584.abstract
AB DNA damage tolerance pathways are regulated by proliferating cell nuclear antigen (PCNA) modifications at lysine 164. Translesion DNA synthesis by DNA polymerase η (Polη) is well studied, but less is known about Polη-independent mechanisms. Illudin S and its derivatives induce alkyl DNA adducts, which are repaired by transcription-coupled nucleotide excision repair (TC-NER). We demonstrate that in addition to TC-NER, PCNA modification at K164 plays an essential role in cellular resistance to these compounds by overcoming replication blockages, with no requirement for Polη. Polκ and RING finger and WD repeat domain 3 (RFWD3) contribute to tolerance, and are both dependent on PCNA modifications. Although RFWD3 is a FANC protein, we demonstrate that it plays a role in DNA damage tolerance independent of the FANC pathway. Finally, we demonstrate that RFWD3-mediated cellular survival after UV irradiation is dependent on PCNA modifications but is independent of Polη. Thus, RFWD3 contributes to PCNA modification–dependent DNA damage tolerance in addition to translesion DNA polymerases.